This invention relates generally to drug-delivery devices, and more specifically to intravascular catheters for delivery of therapeutic agents from within a lumen of a blood vessel or other body organ.
In percutaneous transluminal angioplasty procedures, a catheter having an expandable distal end, usually in the form of a balloon, is positioned in a lumen of a blood vessel with the distal end disposed within a stenotic atherosclerotic region of the vessel. The expandable end is then expanded to dilatate the vessel and restore adequate blood flow through the region of stenosis.
Whereas angioplasty has gained wide acceptance, it continues to be plagued by two major problems, abrupt closure and restenosis. Abrupt closure refers to the acute occlusion of a vessel immediately after or within the initial hours following the dilatation procedure. This type of complication, occurring in approximately one in twenty cases, frequently results in myocardial infarction and death if blood flow is not quickly restored. The primary mechanisms of abrupt closures are arterial dissection and/or thrombosis. It is postulated that the ability to deliver agent (e.g. an antithrombotic drug) directly into the arterial wall at the time of angioplasty would reduce the incidence of thrombotic acute closure.
Restenosis refers to the re-narrowing of an artery after an initially successful angioplasty. Restenosis usually occurs within the initial six months after angioplasty. It is postulated that the delivery of certain agents directly into the arterial wall would interrupt the cellular events leading to restenosis.
The potential utility of local intramural drug delivery is not limited to atherosclerotic coronary artery disease. Other sites of atherosclerosis (e.g. renal, iliac, femoral, distal leg and carotid arteries as well as saphenous vein grafts, synthetic grafts and arteriovenous shunts used for hemodialysis) would also be appropriate for local intramural drug delivery. Local intramural therapy may also prove efficacious in non-arterial structures, including the prostate via the prostatic urethra (benign prostatic hypertrophy, prostatitis and adenocarcinoma), fallopian tubes via its lumen (strictures), and brain parenchyma (Parkinson's Disease).
At present, intravenous medications are delivered systemically by vein or regionally (e.g. intracoronary infusion). Systemic delivery is generally not well suited to the treatment of disease entities with a single site or several discrete sites of interest (e.g., coronary artery disease) in that it necessitates: (1) exposing sites other than the site of interest to medication where it may have an adverse effect; (2) infusing sufficient quantities of agent to achieve the concentration throughout the entire volume of distribution; and (3) exposing the agent to degradation and elimination by one or more organ systems remote from the site of interest. Furthermore, the tissue concentration that can be achieved at the site of interest is often limited by the effects of the agent at distant sites. Local intramural delivery obviates these problems. Therefore, it is of particular importance to deliver the therapeutic agent directly to the treatment site by contact with or penetration into the tissue, rather than simply releasing the agent into the blood stream in the vicinity of the treatment site.
While various catheters have been developed for delivery of agents to a treatment site within a vessel or organ lumen, such devices have suffered from certain drawbacks. In particular, known agent delivery catheters generally do not permit delivery of an agent directly to a treatment site independently of the deployment of the delivery mechanism adjacent the lumen wall. For example, known agent delivery catheters frequently employ an expandable member such as a balloon which is expanded near the treatment site and brought into contact with the lumen wall. A therapeutic agent is usually delivered through pores on the surface of the balloon. In such devices, the pressurized fluid which expands the balloon is also the vehicle for the agent. Therefore, the balloon cannot be expanded without expelling the drug/vehicle mixture. This scheme is inefficient, in that agent is expelled before the periphery of the balloon is adjacent to the lumen wall. This scheme also prevents delivery of agent without at least partly expanding the balloon. The deployment mechanism (i.e. balloon expansion) and the drug delivery mechanism are inextricably linked.
Thus, where it would be desirable to dilatate a region of stenosis in an artery without simultaneously infusing an agent, known drug delivery catheters are of little use. Moreover, where it would be desirable to infuse an agent within a body lumen without deploying the balloon, known drug delivery catheters are similarly ineffective. Furthermore, in devices which employ the agent/vehicle mixture to pressurize and expand the balloon, the reversal of fluid flow required to retract the balloon tends to draw blood into the device, preventing further use of the device until the blood has been expelled. Typically, this prevents multiple treatments without withdrawing the catheter for purging or replacement.
A further drawback of known drug delivery devices stems from their incapacity for selective delivery of agent to various sectors of an organ lumen. Such directional treatment may be advantageous, where, for example, only a particular portion of a vessel wall is diseased and infusion to non-diseased regions is undesirable. Further, in certain procedures, the ability to selectively infuse different agents in different areas of the lumen may be advantageous. In known devices, it is not possible to deliver agent selectively into a particular sector of the artery, or to deliver two or more different agents into different sectors simultaneously.
Moreover, known drug delivery catheters which infuse an agent through a porous balloon generally release the agent at relatively low pressures so as to merely bathe or coat the vessel wall where it is contacted by the infusion member. With such devices, the agent will generally not penetrate the lumen wall and may not provide effective therapy. Treatment would be more effective if the therapeutic agent were delivered at pressures sufficient to achieve penetration to the adventitial layer of the organ wall.
A drug delivery catheter is therefore desired which can be used to administer therapeutic agents to a treatment site within a lumen of a body organ by direct contact with the lumen wall tissue. Most desirably, the drug delivery catheter will be deployable against the treatment site independently of the delivery of the agent to the site. The catheter should also allow dilatation of a vessel with or without delivery of a drug or other therapeutic agent. Preferably, the catheter should be capable of injecting an agent at pressures sufficient to penetrate the adventitial layer of an artery. In addition, the catheter should allow selective infusion of an agent in various radial directions, and simultaneous infusion of two or more different agents in different radial directions. The catheter should further be useful for treatment of blood vessels as well as a variety of other body organs.